The overall goal of this project is to develop and validate novel approached to quantify local myocardial perfusion and flow reserve using intrinsic NMR contrast and to determine the utility of these techniques in detecting coronary artery disease (CAD). Recent advances in NR technology and recent discoveries regarding contributions to MR image contrast may allow minimally or completely non-invasive measurement of heart perfusion and local myocardial work. Experiments supported by this PPG and others have demonstrated that changes in flow and blood oxygenation affect the longitudinal (T1) and transverse (T2) relaxation times in the heart. Perfusion changes directly alter T1. Changes in venous blood oxygenation, derived from the coupling between flow and function, alter T2. Though some of the earlier work on the brain (Projects 1) can be extended to the heart, cardiac studies are uniquely challenging because of the general problem of measuring small changes in a constantly moving organ. The relationship between the intrinsic NMR changes and the underlying physiology is complicated by a variety of other microscopic and macroscopic processes. This research will investigate several of these effects including the role intra/extra- vascular water exchange, the use of magnetization transfer effects of T1 measures of flow, the changing magnetic environment as the heart beats; and artifactual changes at longer echo times due to flow dephasing on myocardial image contrast. We seek to exploit these changes to produce quantitative maps of the results of pharmacological stress using vasodilatory (adenosine and dobutamine) challenge in intact porcine models of coronary artery stenosis and myocardial stunning. We hypothesize that the degree of local T1 and T2*-weighted image enhancement during vasodilation correlates directly with the local change in microsphere-measured flow. Studies will then be performed in patients with suspected CAD using adenosine challenge to determine the sensitivity of intrinsic NMR contrast for detecting physiologically significant CAD compared to N13 ammonia PET measurements.